The Role Of MicroRNA-183Family In The Pathogenesis And Development Of Noise-induced Deafness

The chronic hearing loss and cochlear mechanical damage caused by noise areclosely related with metabolic disorders. Continue to work in hazardousindustrial-noise environment, over stimulate with noise in a long period of time oftencan cause the cochlear hair cells necrosis or apoptosis. The activity enhancement ofoxygen free radical and energy metabolism disorder in cochlear hair cells areconsidered the major cause of the inner ear hair cells’ necrosis or apoptosis.With thedeepening of the mechanism of noise deafness, the researchers found that the onset ofnoise deafness has both environmental and genetic factors.The role of miRNA in organism development has been extensive research, andthe role of many high conservative miRNA in certain cells, organs, and biologicalprocesses (including disease) has been fully understood. MiR-183family has anamount of expression and plays an important regulatory role in the inner ear. It alsohas a close relation with hearing loss. Therefore, the correlation between miR-183family and hearing loss will become a hot research topic, and explore the treatmentat the gene level, especially related to hair-cell regeneration areas and the hearingimprovement, etc. Thus, miR-183family has immeasurable scientific value in thefield of audiology, as well as opens up a new light way in the human hearing.In this topic, the mice were exposed to2～4KHz narrow band noise at100dBSPL6h per day for3consecutive days. Detect the degree of damage in inner ear haircells with the noise-induced hearing loss, and the expression changes of miR-183family members before and after cochlear hearing loss, in order to further elucidatethe pathogenesis of the noise-induced hearing loss, and provides new train of thoughtfor the future treatment of the noise-induced hearing loss. This article altogether isdivided into three parts. PartⅠ Establishment of an animal model of noise-inducedhearing lossObjective To establish an animal model of noise-induced hearing loss, and toresearch the degree of damage in inner ear hair cells, and to lay the foundation for thedetection in the expression changes of miR-183family members before and afternoise-induced hearing loss.Methods50mice were randomly divided into5groups. In the experimentalgroup,40mice were exposed to2～4KHz narrow band noise at100dB SPL6h perday for3consecutive days. The rest10mice served as the control group withoutreceiving any noise. To assess hearing threshold shift,auditory brainstem response(ABR) were examined at the1st,7th,14th, and28th day before and after noiseexposure.Results The minimum stimulus intensity that can distinguish the wave IorⅡwas used to assess ABR threshold, And repeat twice.After noise exposurefor1,7,14,28days, the average ABR threshold were62.50±3.80dB、44.50±4.56dB、40.25±4.13dB、40.50±3.20dB respectively,Statistical analysis revealed that therewere statistically significant differences(P<0.01) before and after noise exposure inthe experimental group. After the noise stimulation,There was statistically significantdifference (P<0.01) between the experimental group and the control. There werestatistically significant differences (P<0.01) among the group of1st day after noiseexposure and the group of the7th,14th, and28th day, and there were statisticallysignificant differences (P<0.05) among the group of7th day after noise exposure andthe group of the14th and28th day, while there was no statistically difference(P>0.05)between the group of14th and28th day.Conclusion The intense noise used in our study can cause permanent hearingthreshold shift in mice. We successfully established an animal model of noise-inducedhearing loss. Laying the foundation for the study of the pathogenesis in noise-inducedhearing loss. Part Ⅱ The study of hair cells in noise-induced hearing lossObjective Detect the degree of damage in hair cells with the noise-inducedhearing loss, to determine that the noise damage hearing through damaging the haircells.Methods Groups of mice were beheaded quickly after anesthesia, and tookbilateral auditory vesicle. Stained with0.5%silver nitrate solution, and thenprocessed the surface preparation techniques of the cochlear basilar membrane,observed the damage of the hair cells.Results There were three rows of out hair cells (OHC) and a row of inner haircells (IHC) on the second The second section of cochlear basilar membrane. Theywere ordered, dyed with low loss rate. The outside cilia cluster was inverted "v"shape, and the inside cilia cluster was inverted "u" shape. The IHCs of1st day groupwere arranged in alignment, OHCs were arranged disorder, and their sizes were differ,but the loss was less. The IHCs of7th day group were arranged in alignment, and sawa small amount of missing in OHCs. The OHCs of14th day group had obvious defect,and the defect were mainly concentrated in the first and second row. The IHCs of28th day group were arranged in alignment, but the OHCs were saw a lot of missing.Conclusion The degree of noise can damage the hair cell in inner ear. Thedamage to the hair cells may be an early pathological changes of the noise-inducedhearing loss in mice, and this process will continue until at least28days. Mainlydestroied is the OHCs, and more concentrated in the first and second row.Part Ⅲ The expression and research of miR-183family in thenoise-induced hearing lossObjective To detect the expression changes of miR-183family membersbefore and after cochlear hearing loss, and to investigate whether the miR-183family is involved in the regulatory mechanism of strong noise induced cochlear celldestruction. In order to further elucidate the pathogenesis of the noise-inducedhearing loss. Methods Using real-time quantitative polymerase chain reaction (qRT-PCR)to detect expression changes of miR-183family members. Analyze the data usingSPSS17.0software.Results The qRT-PCR showed that the expressions of the three genes(miR-183/96/182)in the1st day and7th day group with exposure to noise were lowerthan in the control group（P<0.01),while no significant difference was found between1st day and7th day group (P>0.05).The expressions began to rise at the14th daygroup in the experimental groups, whereas at the28th day group the expressions ofthe three genes decrease markedly which were higher than in the1st day and7th daygroup（P<0.01).Conclusion After noise exposure for some time, the expressions of miRNA-183family members experience significant change in animal model with thenoise-induced hearing loss, which may play an important role in the pathogenesis anddevelopment of the noise-induced hearing loss.